DR. PHILLIP SWARTZ A&P II METABOLISM Page 144

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1 DR. PHILLIP SWARTZ A&P II METABOLISM Page 144 Nutrients are chemical substances in food that provide energy, form new body components, or assist in the functioning of various body processes. There are six principal classes of nutrients - carbohydrates, lipids, proteins, minerals, vitamins, and water. The end products of digestion that ultimately reach body cells are monosaccharides, amino acids, fatty acids, glycerol, and monoglycerides. Some are used to synthesize new structural molecules in cells or to synthesize new regulatory molecules such as hormones and enzymes. Most are used to produce energy to sustain life processes. This energy is used for processes such as active transport, DNA replication, synthesis of proteins in other molecules, muscle contraction, and nerve impulse conduction. Until the energy is needed, it is stored in ATP. Some minerals and many vitamins are part of enzyme systems that catalyze reactions undergone by carbohydrates, proteins, and lipids. Water has five major functions. It is an excellent solvent and suspending medium, it participates in hydrolysis reactions, it acts as a coolant, it lubricates, and it helps to maintain a constant body temperature due to its ability to release and absorb heat slowly. Metabolism refers to all the chemical reactions of the body. The body's metabolism may be thought of as an energy balancing act between anabolic or synthetic and catabolic or degradative reactions. In living cells those chemical reactions that combine simple substances into more complex molecules are collectively known as anabolism. An anabolic process requires energy which is supplied by catabolic reactions. The chemical reactions that break down complex organic compounds into simple ones are collectively known as catabolism. Catabolic reactions release the available chemical energy in organic molecules. This energy is then stored in ATP. Catabolic reactions release energy that can be used to drive anabolic reactions.

2 DR. PHILLIP SWARTZ A&P II METABOLISM Page 145 Oxidation - Reduction Reactions Oxidation is the removal of electrons and hydrogen ions (hydrogen atoms) from a molecule or, less commonly, the addition of oxygen to a molecule. Most oxidations are actually dehydrogenations, that is, they involve the loss of hydrogen atoms. An example of an oxidation is the conversion of lactic acid into pyruvic acid. When a substance is oxidized, the free hydrogen atoms are transferred to another compound by substances that work with enzymes called coenzymes. Reduction is the addition of electrons and hydrogen ions or hydrogen atoms to a molecule or, less commonly, the removal of oxygen from a molecule. Reduction is the opposite of oxidation. An example of reduction is the conversion of pyruvic acid into lactic acid. Within a cell oxidation and reduction reactions are always coupled. That is, whenever a substance is oxidized another is almost simultaneously reduced. This coupling of reactions is simply referred to as oxidation-reduction. Oxidation is usually an energy-producing reaction. Cells take nutrients (energy sources) and degrade them from highly reduced compounds with many hydrogen atoms to highly oxidized compounds with many oxygen atoms or multiple bonds. In body cells enzymes service catalysts that speed up chemical up chemical reactions by increasing the frequency of collision, lowering activation energy, and properly orienting colliding molecules. A catalyst is a chemical substance that alters the rate of a chemical reaction without becoming part of the products of the reaction or being used up. Enzymes speed up chemical reactions without an increase in temperature or pressure, changes that could seriously disrupt or kill cells. All enzymes are proteins. Enzymes are extremely efficient as catalysts of biochemical reactions. Enzymes are very specific in the reactions they catalyze and the molecules with which they react. Such molecules are called substrates. Enzymes are also subject to various controls by the cellular machinery. Their rate of synthesis at any given time is under the control of the cells' genes and is influenced by various other molecules in the cell. The names of enzymes usually end in the suffix - ase.

3 DR. PHILLIP SWARTZ A&P II METABOLISM Page 146 Some enzymes consist only of proteins. Most enzymes, however, contain a protein called an apoenzyme that is inactive without a nonprotein component called the cofactor. Together the apoenzyme and cofactor are an activated holoenzyme, or whole enzyme. If the cofactor is removed, the apoenzyme will not function. The cofactor can be a metal ion or a complex organic molecule called a coenzyme. Iron, magnesium, zinc, and calcium are metal ions that serve as cofactors. Many coenzymes are derived from vitamins. Three coenzymes commonly used by living cells to carry hydrogen atoms are nicotinamide, adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP), both of which are derivatives of the B vitamin niacin, and flavin adenine dinucleotide (FAD), a derivative of vitamin B2 (riboflavin). Enzymes lower the activation energy. The surface of the substrate makes contact with a specific region on the surface of the enzyme molecule known as the active site. A temporary intermediate compound called an enzyme substrate complex forms. The substrate molecule is transformed and the transformed substrate molecules now called the products of the reaction move away from the enzyme molecule. After the reaction is completed, the products of the reaction move away from the enzyme and the enzyme is free to attach to another substrate molecule. Concerning carbohydrate metabolism, glucose is the body's preferred source of energy and the fate of absorbed glucose depends on the body cells' energy needs. Before glucose can be used by body cells it must first pass through the plasma membrane and then enter the cytoplasm. The process by which this occurs is facilitated diffusion and the rate of glucose transport is greatly increased by insulin. Immediately upon entry into cells, glucose combines with a phosphate group produced by the breakdown of ATP. This addition of a phosphate group to a molecule is called phosphorylation. The oxidation of glucose is also known as cellular respiration. It occurs in every cell in the body and provides the cells' chief source of energy. The complete oxidation of glucose to carbon dioxide and water produces large amounts of energy. It occurs in three successive stages - glycolysis, the Kreb's cycle, and the electron transport chain.

4 DR. PHILLIP SWARTZ A&P II METABOLISM Page 147 The term glycolysis refers to a series of chemical reactions in the cytoplasm of a cell that convert a six-carbon molecule of glucose into two three-carbon molecules of pyruvic acid, Under aerobic conditions, the process of the complete oxidation of glucose continues and pyruvic acid is oxidized to form carbon dioxide and water in two sets of reactions: the Kreb's cycle and the electron transport chain. This is known as aerobic respiration. However, before pyruvic acid can enter the Kreb's cycle, it must be prepared. This process occurs in mitochrondia. Formation of Acetyl coenzyme A Each step in the oxidation of glucose requires a different enzyme and often a coenzyme as well. We are interested in only one coenzyme at this point, a substance called Coenzyme A (CoA), which contains a derivative of pantothenic acid, a B vitamin. During the transitional step between glycolysis and the Kreb's cycle, pyruvic acid is prepared for entrance into the cycle. Essentially, pyruvic acid is converted to a two-carbon compound by the loss of carbon dioxide. The loss of a molecule of CO2 by a substance is called decarboxylation. This two-carbon fragment called an acetyl group attaches itself to coenzyme A and the whole complex is called acetyl coenzyme A. This substance is now prepared to enter the Kreb's cycle. Kreb's Cycle The Kreb's cycle is also called the citric acid cycle, or the tricarboxyclic acid cycle (TCA). It is a series of reactions that occur in the matrix of mitochrondia of cells. Coenzyme A carries an acetyl group to a mitochondrian, detaches itself, and goes back into the cytoplasm to pick up another fragment. The acetyl group combines with oxaloacetic acid to form citric acid. From this point the Kreb's cycle consists mainly of a series of decarboxylation and oxidation-reduction reactions, each controlled by a different enzyme.

5 DR. PHILLIP SWARTZ A&P II METABOLISM Page 148 Each time a molecule of pyruvic acid enters the Kreb's cycle, four molecules of NADH2 and one molecule of FADH2 are produced by the various oxidation-reduction reactions. These reduced coenzymes are very important because they now contain the stored energy originally in glucose and then in pyruvic acid. In the next stage in the complete oxidation of glucose, the electron transport chain, the energy in the coenzymes is transferred to ATP for storage. Electron Transport Chain The electron transport chain is a series of oxidation-reduction reactions that occur on mitochrondial cristae in which the energy in NADH2 and FADH 2 is liberated and transferred to ATP for storage. In the electron transport chain three types of carrier molecules are alternately oxidized and reduced and participate in the generation of ATP: (1) The coenzyme FAD (2) A coenzyme called coenzyme Q (ubiquinone) (3) Cytochromes - red protein pigments that have an iron-containing group capable of alternating between a reduced form (Fe ++ ) and an oxidized form (Fe +++ ) Because of the involvement of cytochromes in the electron transport chain, it is also known as the cytochrome systen}. Most of the glucose in the body is catabolized to supply energy. However, some glucose participates in the number of anabolic reactions. One is the synthesis of glycogen from many glucose molecules. Another is the manufacture of glucose from the breakdown products of proteins and lipids. Glucose Storage (Glycogenesis) If glucose is not needed immediately for energy, it is combined with many other molecules of glucose to form a long-chain molecule called glycogen. This process is called glycogenesis. Glycogen is stored in the liver and in skeletal muscles.

6 DR. PHILLIP SWARTZ A&P II METABOLISM Page 149 Glucose Release (Glycogenolysis) When the body needs energy, the glycogen stored in the liver is broken down into glucose and released into the blood stream to be transported to cells where it will be catabolized. The process of converting glycogen back to glucose is called glycogenolysis. Glycogenolysis usually occurs between meals. Formation of Glucose from Proteins and Fats (Gluconeogenesis) When your liver runs low on glycogen it is time to eat. If you do not eat your body starts catabolizing fats and proteins. Both fat molecules and protein molecules may be converted in the liver to glucose. The process by which glucose is formed from noncarbohydrate sources is called gluconeogenesis. Gluconeogenesis is stimulated by cortisol, one of the glucorticoid hormones of the adrenal cortex and thyroxine from the thyroid gland. Cortisol mobilizes proteins from body cells making them available in the form of amino acids, thus supplying a pool of amino acids for gluconeogenesis. Thyroxine also mobilizes proteins and may mobilize fats from fat depots by making glycerol available for gluconeogenesis. Gluconeogenesis is also stimulated by epinephrine, glucagon, and growth hormone. Lipids are second to carbohydrates as a source of energy. The major function of adipose tissue is to store fats until they are needed for energy in other parts of the body. Fat also insulates and protects. Fats stored in adipose tissue constitute the largest reserve of energy. The body can store much more fat than it can glycogen. Moreover, the energy yield of fats is more than twice that of carbohydrates. Fatty acids are catabolized differently and the process occurs in the matrix of mitochrondia. The first step in fatty acid catabolism involves a series of reactions called beta oxidation. Through a series of complex reactions involving dehydration, hydration, and cleavage, enzymes remove pairs of carbon atoms at a time from the long chain of carbon atoms comprising a fatty acid. The result of beta oxidation is a series of two-carbon fragments acetyl coenzyme A (CoA).

7 DR. PHILLIP SWARTZ A&P II METABOLISM Page 150 As part of normal fatty acid catabolism, the liver can take acetyl coenzyme A molecules two at a time and condense them to form a substance called acetoacetic acid which is converted mostly into B-hydroxybutyric acid and partially into acetone. These substances are collectively known as ketone bodies and their formation is called ketogenesis. They then leave the liver, enter the bloodstream, and diffuse into other body cells where they are broken down into acetyl coenzyme A which enters the Kreb's cycle for oxidation. Lipid Anabolism (Lipogenesis) Liver cells can synthesize lipids from glucose or amino acids through a process called lipogenesis. Lipogenesis occurs when a greater quantity of carbohydrate enters the body than can be used for energy or stored as glycogen. The excess carbohydrate is synthesized into fats. Protein Metabolism During the process of digestion, proteins are broken down into their constituent amino acids. The amino acids are then absorbed by the blood capillaries and villi and transported to the liver via the hepatic portal vein. Amino acids enter body cells by active transport. A certain amount of protein catabolism occurs in the body each day, although much of this is only partial catabolism. Before amino acids can be catabolized, they must first be converted to various substances that can enter the Kreb's cycle. One such conversion consists of removing the amino group (NH2) from the amino acid, a process called deamination. The liver cells then convert the NH2 to amonia (NH3) and finally to urea which is excreted in the urine. Protein Anabolism Protein anabolism involves the formation of peptide bonds between amino acids to produce new proteins. Protein anabolism or synthesis is carried out on the ribosomes of almost every cell in the body, directed by the cells' DNA and RNA.

9 DR. PHILLIP SWARTZ A&P II METABOLISM Page 152 Regulation of Metabolism Absorbed nutrients have several alternatives based upon the needs of the body. They may be oxidized for energy, stored, or converted. Hormones are the primary regulators of metabolism. However, hormonal control is ineffective without the proper minerals and vitamins. Minerals are inorganic substances. They may appear in combination with each other or in combination with organic compounds. Minerals constitute about 4% of the total body weight and they are concentrated most heavily in the skeleton. Minerals known to perform functions essential to life include calcium, phosphorous, sodium, manganese, cobalt, copper, zinc, selenium, and chromium. Vitamins Organic nutrients required in minute amounts to maintain growth and normal metabolism are called vitamins. Unlike carbohydrates, fats or proteins, vitamins do not provide energy or serve as building materials. The essential function of vitamins is the regulation of physiological processes. Of the vitamins whose functions are known, most serve as coenzymes. Most vitamins cannot be synthesized by the body. They may be ingested in foods or pills. The body can assemble some vitamins if the raw materials called provitamins are provided. The term avitaminosis refers to a deficiency of any vitamin in the diet. Hypervitaminosis refers to an excess of one or more vitamins. Hypovitaminosis refers to a deficiency of one or more vitamins. On the basis of solubility, vitamins are divided into two principal groups, fat soluble and water soluble. Heat is a form of energy that can be measured as temperature and expressed in units called calories. A calorie is the amount of heat energy required to raise the temperature of one gram of water one degree celsius. Since the calorie is a small unit and large amounts of energy are stored in foods, the kilocalorie is used instead. A kilocalorie is equal to 1,000 calories and is defined as the amount of heat required to raise the temperature of 1,000 grams of water one degree celsius. The apparatus used to determine the caloric value of foods is called a calorimeter.

10 DR. PHILLIP SWARTZ A&P II METABOLISM Page 153 Most of the heat produced by the body comes from oxidation of the food we eat. The rate at which this heat is produced, known as the metabolic rate, is also measured in kilocalories. Among the factors that affect metabolic rate are the following: exercise, nervous system, hormones, body temperature, ingestion of food, and age. Since many factors affect metabolic rate, it is measured under standard conditions designated to reduce or eliminate those factors as much as possible. These conditions of the body are called the basal state and the measurement obtained is the basal metabolic rate or BMR. The person should not exercise for 30 to 60 minutes before the measurement is taken. The individual must be completely at rest but awake. Body heat is produced by the oxidation of foods we eat. This heat must be removed continuously or body temperature would rise steadily. The principal routes of heat loss include radiation, conduction, convection, and evaporation. If the amount of heat production equals the amount of heat loss, you maintain a constant body temperature near 37 degrees celsius or 98.6 degrees Fahrenheit. Body temperature is regulated by mechanisms that attempt to keep heat production and heat loss in balance. A center of control of these mechanisms is found in the hypothalamus in a group of neurons near the anterior portion referred to as the preoptic area. Some disorders and clinical terms include: 1. Fever - an abnormally high body temperature. Any substances of capable of producing fever are called exogenous pyrogens. Exogenous pyrogens cause certain phagocytes, namely monocytes and macrophages to synthesize small proteins called endogenous pyrogens. Endogenous pyrogens circulate to the anterior hypothalamus and induce neurons of the preoptic area to secrete prostaglandins. 2. Even when body temperature is climbing higher than normal, say 38.3 degrees Celsius or 101 degrees Fahrenheit, the skin remains cold and shivering occurs. This condition called a chill is a definite sign that body temperature is rising.

11 DR. PHILLIP SWARTZ A&P II METABOLISM Page Heat cramps occur as a result of profuse sweating that removes water and salt from the body. 4. Heat stroke or sunstroke is brought about when the temperature and relative humidity are high, making it difficult for the body to lose heat by radiation or evaporation. As a result, there is a decreased flow of blood to the skin, perspiration is greatly reduced, and body temperature rises sharply. 5. Heat exhaustion or heat prostration - The body temperature is generally normal or a little below normal and the skin is cool and clamy (moist) due to profuse perspiration. 6. Obesity is defined as a body weight 10% to 20% above a desirable standard as a result of an excessive accumulation of fat. 7. Phenylketonuria (PKU) is a genetic error of metabolism characterized by an elevation of the amino acid phenylalanine in the blood. It is frequently associated with mental retardation. 8. Cystic Fibrosis is an inherited disease of the exocrine glands that affects the pancreas, respiratory passageways, and salivary and sweat glands. It is the most common lethal genetic disease of Caucasians. 5% of the population are thought to be genetic carriers. The cause of cystic fibrosis has recently been linked to an inability of chloride ions to cross epithelial cells in affected regions of the body. Among the most common signs and symptoms are pancreatic insufficiency, pulmonary involvement, and cirrhosis of the liver. It is characterized by the production of thick exocrine secretions that do not drain easily from the respiratory passageways. 9. Celiac Disease results in malabsorption by the intestinal mucosa due to the ingestion of gluten. Gluten is the water insoluble protein fraction of wheat, rye, barley, and oats. In susceptible persons, ingestion of gluten induces destruction of villi and inhibition of enzyme secretion accompanied by a variable amount of malabsorption. The condition is easily remedied by administering a diet that excludes all cereal grains except rice and corn.

12 DR. PHILLIP SWARTZ A&P II METABOLISM Page Kwashiorkor - Some dietary proteins are referred to as complete proteins, that is, they contain adequate amounts of essential amino acids. Sources of complete proteins are primary animal products such as milk, meat, fish, poultry, and eggs. Incomplete proteins lack essential amino - acids. An example is zein, the protein in corn, which lacks the essential amino acids tryptophan and lysine. The diet of many African natives consists largely of cornmeal. As a result, many African children especially develop a protein deficiency called Kwashiorkor. It is characterized by hypoprotein edema of the abdomen, lethargy, failure to grow, and sometimes mental retardation.

Energy Production In A Cell (Chapter 25 Metabolism)

Energy Production In A Cell (Chapter 25 Metabolism) Large food molecules contain a lot of potential energy in the form of chemical bonds but it requires a lot of work to liberate the energy. Cells need